Long-term endurance sports are associated with atrial remodeling and an increased risk for atrial fibrillation (AF) and atrial flutter. Pro-atrial natriuretic peptide (pro-ANP) is a marker of atrial wall tension and elevated in patients with AF. The aim of this study was to test the hypothesis that atrial remodeling would be perpetuated by repetitive episodes of atrial stretching during strenuous competitions, reflected by elevated levels of pro-ANP. A cross-sectional study was performed on nonelite runners scheduled to participate in the 2010 Grand Prix of Bern, a 10-mile race. Four hundred ninety-two marathon and nonmarathon runners applied for participation, 70 were randomly selected, and 56 entered the final analysis. Subjects were stratified according to former marathon participations: a control group (nonmarathon runners, n = 22), group 1 (1 to 4 marathons, n = 16), and group 2 (≥5 marathons, n = 18). Results were adjusted for age, training years, and average weekly endurance training hours. The mean age was 42 ± 7 years. Compared to the control group, marathon runners in groups 1 and 2 had larger left atria (25 ± 6 vs 30 ± 6 vs 34 ± 7 ml/m(2), p = 0.002) and larger right atria (27 ± 7 vs 31 ± 8 vs 35 ± 5 ml/m(2), p = 0.024). Pro-ANP levels at baseline were higher in marathon runners (1.04 ± 0.38 vs 1.42 ± 0.74 vs 1.67 ± 0.69 nmol/L, p = 0.006). Pro-ANP increased significantly in all groups after the race. In multiple linear regression analysis, marathon participation was an independent predictor of left atrial (β = 0.427, p <0.001) and right atrial (β = 0.395, p = 0.006) remodeling. In conclusion, marathon running was associated with progressive left and right atrial remodeling, possibly induced by repetitive episodes of atrial stretching. The altered left and right atrial substrate may facilitate atrial arrhythmias.